Reversible addition–fragmentation chain-transfer polymerization was introduced to prepare a series of zwitterionic poly(hydroxyethyl methacrylate)-g-poly(sulfobetaine methacrylate) (PSBMA) hydrogels (HSGs) with different monomer feed ratios. Compared with PSBMA hydrogels, these hydrogels exhibited enhanced mechanical strengths. Then, the HSGs were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and swelling measurements. We found that the equilibrium swelling ratios, mechanical strengths, and drug-release behaviors were significantly affected by the feed ratios of the gels. The hydrophilic tetracycline hydrochloride release results suggest that the hydrophilic drug release from the HSGs could be prolonged by the variation of the hydroxyethyl methacrylate amount in the gel networks. The bovine serum albumin adsorption data showed that the zwitterionic HSG with 18.2 wt % sulfobetaine methacrylate exhibited good protein-resistance properties. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41041.